Lung cancer is one of the most common but serious cancers in the world. Both the X-ray repair cross-complementing group 1 (XRCC1) gene and the human multidrug resistance 1 (MDR1) gene are important candidate genes influencing the susceptibility to various diseases, including lung cancer. This study aimed to assess the correlation of genetic polymorphisms in XRCC1 and MDR1 with the susceptibility to lung cancer. In this study, a total of 320 lung cancer patients and 346 cancer-free controls in Chinese population were enrolled in this study. Data about the clinical characteristics and related risk factors of lung cancer were collected by questionnaires. The single-nucleotide polymorphisms (SNPs) of XRCC1 and MDR1 genes were genotyped by created restriction site-polymerase chain reaction method. Our data showed that the risk for lung cancer increased significantly among the variant Arg194Trp (C > T, rs1799782) and Arg399Gln (G > A, rs25487) of XRCC1, but there are no significant differences in the allelic and genotypic frequencies of c.1564A > T and c.3073A > C of MDR1 between lung cancer patients and cancer-free controls. In conclusion, these preliminary results suggest that the C > T, rs1799782 and C > T, rs25487 of XRCC1 genetic variants might be used as molecular markers for detecting lung cancer susceptibility.